The aim of the proposed research is to investigate some aspects of the basic mechanisms by which prostatic growth is controlled by hormones. The development of both benign prostatic hyperplasia and prostatic carcinoma is dependent on the presence of functioning testes, and many patients with carcinoma experience regression of the disease when serum androgen levels are lowered by castration or estrogen treatment. Using surgical specimens of human prostate, we are currently investigating the concentration and some of the physio-chemical properties of macromolecular proteins which bind androgens with high affinity (androgen receptors) which have been demonstrated in all androgen target organs so far investigated, and which are related to hormonal sensitivity. So far, our work has been restricted to the investigation of androgen receptor in the cytosolic fraction of the prostate gland. However, since the site of action of the hormone receptor complex is nuclear, investigation of cytosol receptor alone gives an incomplete picture of the initial events which ultimately result in hormonal stimulation. Investigation of nuclear binding capacity may give a more accurate assessment of hormonal sensitivity. The methods so far used for the estimation of nuclear binding capacity for androgen in the prostate fall into two groups: the first, which examines androgen binding to a nuclear salt extract, has been used most commonly. Very few investigations on human prostate have used the second approach, which involves tissue incubation, and which probably represents the physiological situation more closely in that it also measures translocation of the hormone-receptor complex across the nuclear membrane. It is generally assumed that in the untreated subject the two methods give equivalent results, but no direct comparisons have been published. I therefore propose to compare results obtained by both methods (both in animal models and in human tissue), and to examine the inter-relationships between (1) cytosol and nuclear binding capacity (2) the effect of therapy, and wherever possible, (3) the response to therapy.